The purpose of this project is to study the role of the immune system in connective tissue metabolism. We have demonstrated that the prostaglandins control the production of collagenase by endotoxin and lymphokine activated macrophages by regulating the intracellular levels of cyclic nucleotides (cAMP). Additionally, drugs, such as Beta adrenergic stiumlators, dibutyryl cAMP and phosphodiesterase inhibitors, which directly effect cAMP metabolism have been shown to modulate both prostaglandin and collagenase production of endotoxin activated macrophages. High concentration of these cAMP enhancing agents significantly inhibit the production of prostaglandin and collagenase whereas both are stimulated by lower concentrations of these drugs. Studies involving the role of the immune system in bone resorption have revealed that macrophages from an osteopetrotic rat (toothless rat) model are defective in the production of prostaglandins and in the production of suppressors of lymphocyte proliferation. The lower production of prostaglandins by macrophages from the osteopetrotic rats may in part be one of causes for the hyperproliferation of lymphocytes in the animals since prostaglandins are known to suppress lymphocyte proliferation.